Affiliation:
1. Antimicrobials Research Group, Institute of Microbiology and Infection, College of Medical and Dental Science, University of Birmingham , Birmingham, United Kingdom
Abstract
ABSTRACT
The aim of this study was to determine if
acrAB
induction in
Salmonella
Typhimurium relies solely on RamA or if other transcriptional activator pathways are also involved, and to better understand the kinetics of induction of both
acrAB
and
ramA
. We evaluated the expression of
acrAB
in
S
. Typhimurium in response to a variety of compounds that are known to induce the expression of one or more of the transcriptional activators, MarA, SoxS, RamA, and Rob. We utilized green fluorescent protein (GFP) transcriptional reporter fusions to investigate the changes in the expression of
acrAB, ramA, marA,
and
soxS
following exposure to sub-inhibitory concentrations of antimicrobial compounds. Of the compounds tested, 13 induce
acrAB
expression in
S
. Typhimurium via RamA, MarA, SoxS, and Rob-dependent pathways. None of the tested antibiotics induced
acrAB
expression, and compounds that induced
acrAB
expression also induced a general stress response. The results from this study show that the majority of compounds tested induced
acrAB
via the RamA-dependent pathway. However, none of the antibiotic substrates of the AcrB efflux pump directly increased the expression of AcrAB either directly or indirectly via the induction of one of the transcriptional activators. Using a dual GFP/RFP reporter, we investigated the kinetics of the induction of
ramA
and
acrAB
simultaneously and found that
acrAB
gene expression was transient compared to
ramA
gene expression.
ramA
gene expression increased with time and would remain high or decrease slowly over the course of the experiment indicating that RamA exerts a wider global effect and is not limited to efflux regulation alone.
Funder
UKRI | Medical Research Council
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology